Biomedical Engineering Reference
In-Depth Information
gene improved insulin secretion and protected b cell mass by reducing apoptosis
and enhancing proliferation [
75
]. Islets expressing HGF transgene (via adenoviral
gene delivery) showed better outcome after transplantation into streptozotocin-
induced diabetic rats [
76
]. HGF is, therefore, a potential therapeutic agent because
of its beneficial effect on islet mass and function both in vitro and in vivo.
Placental lactogen (PL), prolactin (PRL), and growth hormone (GH) are related
hormones belonging to the same family [
70
]. Lactogenic hormones are involved in
the expansion of b cell mass during pregnancy [
77
]. In vitro treatment of rat, mouse,
and human islets with homologous PRL, PL, and GH enhanced the b cell prolifer-
ation and insulin secretion [
78
,
79
]. In accordance with that, an overexpression of
mouse PL-1 in b cells increased the b cell proliferation by 2-fold [
80
]. Furthermore, a
knockout of PRL or GH receptor led to reduction in b cell mass and insulin secretion
[
81
,
82
]. Lactogens are, therefore, important b cell mitogens that can be utilized at
least in vitro to increase b cell mass, e.g., before islet transplantation.
9.4.3 Role of Nicotinamide
Nicotinamide, a vitamin belonging to vitamin B group, has also been shown to
have beneficial effects in protecting against diabetes. Administration of a high dose
of nicotinamide improved glucose tolerance in NOD mice [
83
]. Nicotinamide
treatment ameliorated the hyperglycemia by expanding the b cell mass following
70 % pancreatectomy in type 2 diabetic rats. However, this effect was sustained
only during the treatment and gradually reversed after the cessation of treatment
[
84
]. Moreover, In vitro treatment of human fetal pancreatic cells with nicotin-
amide increased endocrine differentiation and improved insulin production [
85
].
Considering the beneficial effect of nicotinamide a lot of clinical trials have been
carried out in type 1 diabetic patients; however, the results are variable [
86
-
89
].
Recently, Yoshino et al. [
90
] showed that nicotinamide mononucleotide treatment
can ameliorate glucose intolerance and improve hepatic insulin sensitivity in high-
fat-diet and age-induced type 2 diabetic mice, by restoring the levels of NAD
+
(nicotinamide adenine dinucleotide). The beneficial antidiabetic effect of nico-
tinamide
is,
therefore,
mainly
through
metabolic
improvement
rather
than
enhancement of pancreatic regeneration.
9.4.4 Defeating Autoimmunity to Improve Endogenous
Regeneration in Type 1 Diabetes
As mentioned above, there are a variety of compounds that are potentially helpful
in the treatment of diabetes by improving b cell regeneration and/or function.
However, such treatments, even if they come into clinical practice, are mostly
